into spitting. This reversal of flow is strikingly similar
to a kind of heart disease in which blood flow reverses within the heart called valvular heart disease.

Valvular heart disease is believed to be caused by
valve inflammation and degeneration, but our discovery suggests a potentially new kind of cause for
the disease. In the pharynx, a single neuron seems
to detect a product of light to open a valve, causing
flow reversal and spitting. It’s conceivable that a
similar kind of neuron–or set of neurons–controls
valves in the heart to determine the direction that
blood flows.

Q:If your analogy between the worm’s pharynx and the human heart are confirmed, what
impact could that have on treatments for valvular
heart disease?

A: If what we learned from the worm pharynx also applies to the human heart, it would suggest new kinds of therapy for
valvular heart disease. For example, valvular heart disease might not only be
because of inflammation and degeneration, but also beacuse of dysfunction
of neurons that control heart valves. These neurons might detect toxins or
other molecules in the bloodstream, and when this happens they might try to
stop the spread of such toxins. One way they might do this is by controlling
the valves. If this is true, novel medicines might try to control these neurons,
to keep them from reversing the bloodflow seen in aortic regurgitation and
other valvular heart diseases. This could inspire the next generation of therapies to alleviate suffering and promote health in patients with valvular heart
disease.

Q:Were you surprised by any of your discoveries?

A: We were very surprised to see the worm spit. Very fast cameras have been applied to the study
of feeding before, but because their conditions were
different they had not observed spitting. We were also
surprised to find that spitting was under the control of
only a single neuron, a kind of master controller.

We were also surprised by the simplicity of the
monosynaptic circuit. Though the worm has a minimized
nervous system, we never imagined to discover that the
simplest conceivable neural circuit would function in the
behavioral response to light.

Q:What is the next step for this research?

A: We are excited to be continuing our studies of worm feeding and spitting. We are focusing ourefforts to really understand the neural circuit dynamicsthat control spitting. Might the patterns of neural con-nectivity that we find in this circuit also translate to humans, especially heartand brain function?

We are also studying exactly how spitting might work at the muscular
level. It is well-known that neurons and muscles use calcium to send signals
and contract, respectively. What if spitting were the result of compartmentalized calcium in a single muscle cell? Might this suggest that muscles such
as those found in the heart are capable of more complex contraction and
pumping patterns than previously known? And might this also suggest that
neurons are capable of much more complex operations than previously believed? These are the kinds of questions we are exploring and excited to dig
into. We are also developing software tools to aid both our own research,
and scientists more broadly, which are available at wormweb.org.